PROJECT SUMMARY - RESOURCE The Mutant Mouse Regional Resource Center (MMRRC) at the University of Missouri (MU) provides a unique repository service by importing, storing and distributing mutant mouse strains, cryopreserved germplasm, embryonic stem cells and related reagents as well as performing research to continuously improve the use of mouse models in research. Genetically-engineered mice (GEM, i.e., transgenics, knock-outs and knock-ins) are invaluable to almost all fields of medicine. Tens of thousands of GEM have been created over the last three decades to facilitate better understanding of developmental biology and disease and to test and improve the function of drugs and therapeutics. Since the MMRRC network began, it has evolved into a major resource for the research community with capabilities and a combined inventory of mouse lines and embryonic stem (ES) cells that exceeds the capacity of other mouse repositories worldwide. The overall goal of this proposal is to continue the existing services and expand the functions and capabilities of the MU MMRRC. The specific aims are to 1) provide biomedical investigators with the mouse models and related reagents they require for their research, 2) provide value-added services to aid the biomedical research community, and 3) perform research that has broad application to all models distributed. Over the next five years, the MU MMRRC will continue to rederive imported mice to a pathogen-free state; cryopreserve gametes and embryos; perform genetic and infectious disease monitoring to ensure quality; and distribute live mice, cryopreserved germplasm, tissues, and embryonic stem cells. Research efforts will continue to assess the role of complex gut microbiota in model phenotypes and model reproducibility and translatability by developing well controlled antigen- experienced microbiota, economic strategies by which complex microbiota can be transferred, and tools to better sample microbiota kinetics. These studies will yield new paradigms by which the MMRRC can provide mice (i.e. harboring one or more standardized complex microbiota) and refine value added services that will be made available to the biomedical research community. The MU MMRRC will also continue to transition to a self-sustaining unit by offering an increasing number of services that generate program income. Services include cryopreservation, cryoresuscitation from embryos or sperm, rederivation, genotyping and assay development, marker-assisted genetic analysis for development of speed congenics, karyotyping, colony management, phenotyping, and microbiome manipulation and analysis.